Inclusion Criteria:

• Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to:
  • Follicular lymphoma (FL) G1, G2, or G3a;
  • Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5x109/L at study entry;
  • Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM);
  • Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal).
• Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab-based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following:
  • at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab can be considered a previous regimen in the case the patient responded to it);
  • at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to other PI3K inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or PD after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor.
• Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
• Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal and positive immunofixation test.
• Male or female patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Life expectancy of at least 3 months.
• Availability of fresh tumor tissue and/or archival tumor tissue at Screening.
• Adequate baseline laboratory values as assessed within 7 days before starting study treatment.
• Left ventricular ejection fraction ≥ 50%.

Exclusion Criteria:

• Histologically confirmed diagnosis of follicular lymphoma (FL) grade 3b or transformed disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of transformed disease, a fresh biopsy is recommended.
• Rituximab resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last date of rituximab administration including rituximab maintenance).
• HbA1c > 8.5% at Screening.
• History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator).
• Known lymphomatous involvement of the central nervous system.
• Known history of human immunodeficiency virus (HIV) infection.
• Hepatitis B (HBV) or C (HCV) infection. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
• Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible. CMV PCR test is considered positive if, the result can be interpreted as a CMV viremia according to local SOC.
• Congestive heart failure > New York Heart Association (NYHA) class 2.
• Uncontrolled hypertension despite optimal medical management (per investigator’s assessment).